P
US7622118B2ExpiredUtilityPatentIndex 63

Cancer treatment methods using selected antibodies to aminophospholipids

Assignee: UNIV TEXASPriority: Jul 15, 2002Filed: Aug 15, 2003Granted: Nov 24, 2009
Est. expiryJul 15, 2022(expired)· nominal 20-yr term from priority
Inventors:THORPE PHILIP ERAN SOPHIA
A61K 47/6811A61K 39/395A61K 47/6849C07K 16/2836C07K 2317/24C07K 2317/73A61K 2039/505C07K 16/44A61K 47/62C07K 2317/622C07K 16/18A61K 47/6835C07K 2317/77C07K 2317/732A61K 39/39558
63
PatentIndex Score
3
Cited by
85
References
49
Claims

Abstract

Disclosed are surprising discoveries concerning the role of anionic phospholipids and aminophospholipids in tumor vasculature and in viral entry and spread, and compositions and methods for utilizing these findings in the treatment of cancer and viral infections. Also disclosed are advantageous antibody, immunoconjugate and duramycin-based compositions and combinations that bind and inhibit anionic phospholipids and aminophospholipids, for use in the safe and effective treatment of cancer, viral infections and related diseases.

Claims

exact text as granted — not AI-modified
1. A method for treating an animal with cancer, comprising administering to said animal a therapeutically effective amount of a pharmaceutical composition comprising a purified antibody, or antigen-binding fragment thereof, that comprises at least two variable regions that each comprises three CDRs, wherein said two variable regions are:
 (a) a heavy chain variable region that comprises variable heavy (VH) CDR1, VH CDR2 and VH CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said VH CDR1 has the amino acid sequence of SEQ ID NO:10, said VH CDR2 has the amino acid sequence of SEQ ID NO:11 and said VH CDR3 has the amino acid sequence of SEQ ID NO:12; and 
 (b) a light chain variable region that comprises a variable light (VL) CDR1, VL CDR2 and VL CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said VL CDR1 has the amino acid sequence of SEQ ID NO:13, said VL CDR2 has the amino acid sequence of SEQ ID NO:14 and said VL CDR3 has the amino acid sequence of SEQ ID NO:15. 
 
     
     
       2. The method of  claim 1 , wherein said pharmaceutical composition comprises said antigen-binding fragment of said antibody. 
     
     
       3. The method of  claim 2 , wherein said antigen-binding fragment of said antibody is operatively attached to a human antibody constant region. 
     
     
       4. The method of  claim 1 , wherein said pharmaceutical composition is administered to said animal via intravenous administration. 
     
     
       5. The method of  claim 1 , wherein said antibody or antigen-binding fragment thereof binds to the luminal surface of blood vessels of the vascularized tumor. 
     
     
       6. The method of  claim 1 , wherein an image of the tumor is first obtained by administering to said animal a diagnostically effective amount of a detectably-labeled construct comprising said antibody or antigen-binding fragment thereof operatively attached to a detectable label. 
     
     
       7. The method of  claim 1 , wherein said animal is a human patient. 
     
     
       8. A method for treating an animal with cancer, comprising administering to said animal a therapeutically effective amount of a pharmaceutical composition comprising a purified antibody, or antigen-binding fragment thereof, wherein said antibody comprises at least two variable regions that each comprises three CDRs, wherein said two variable regions are:
 (a) a heavy chain variable region that comprises a variable heavy (VH) CDR1, VH CDR2 and VH CDR3 from the monoclonal antibody 3(14, produced by hybridoma ATCC PTA 4545, wherein said variable heavy (VH) CDR1 has the amino acid sequence of SEQ ID NO:10, said VH CDR2 has the amino acid sequence of SEQ ID NO:11 and said VH CDR3 has the amino acid sequence of SEQ ID NO:12; and 
 (b) a light chain variable region that comprises a variable light (VL) CDR1, VL CDR2 and VL CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said variable light (VL) CDR1 has the amino acid sequence of SEQ ID NO:13, said VL CDR2 has the amino acid sequence of SEQ ID NO:14 and said VL CDR3 has the amino acid sequence of SEQ ID NO:15. 
 
     
     
       9. The method of  claim 8 , wherein said animal is a human patient. 
     
     
       10. A method for treating an animal with cancer, comprising administering to said animal a therapeutically effective amount of a pharmaceutical composition comprising a purified antibody that comprises at least two variable regions that each comprises three CDRs, wherein at least one of said variable regions is:
 (a) a heavy chain variable region from the monoclonal antibody 3G4, produced by bybridoma ATCC PTA 4545, which has the amino acid sequence of SEQ ID NO:2; or 
 (b) a light chain variable region from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, which has the amino acid sequence of SEQ ID NO:4. 
 
     
     
       11. The method of  claim 10 , wherein said animal is a human patient. 
     
     
       12. A method for inhibiting angiogenesis, comprising administering to an animal having a disease associated with angiogenesis a therapeutically effective amount of a pharmaceutical composition comprising a purified antibody, or antigen-binding fragment thereof, that comprises at least two variable regions that each comprises three CDRs, wherein said two variable regions are:
 (a) a heavy chain variable region that comprises variable heavy (VH) CDR1, VH CDR2 and VH CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said VH CDR1 has the amino acid sequence of SEQ ID NO: 10, said VH CDR2 has the amino acid sequence of SEQ ID NO:11 and said VH CDR3 has the amino acid sequence of SEQ ID NO:12; and 
 (b) a light chain variable region that comprises a variable light (VL) CDR1, VL CDR2 and VL CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said VL CDR1 has the amino acid sequence of SEQ ID NO:13, said VL CDR2 has the amino acid sequence of SEQ ID NO:14 and said VL CDR3 has the amino acid sequence of SEQ ID NO:15. 
 
     
     
       13. The method of  claim 12 , wherein said animal has cancer. 
     
     
       14. The method of  claim 12 , wherein said pharmaceutical composition comprises said antigen-binding fragment of said antibody. 
     
     
       15. The method of  claim 14 , wherein said antigen-binding fragment of said antibody is operatively attached to a human antibody constant region. 
     
     
       16. The method of  claim 12 , wherein said animal is a human patient. 
     
     
       17. The method of  claim 12 , wherein said heavy chain variable region has the amino acid sequence of SEQ ID NO:2. 
     
     
       18. The method of  claim 12 , wherein said light chain variable region has the amino acid sequence of SEQ ID NO:4. 
     
     
       19. The method of  claim 12 , wherein said antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region that has the amino acid sequence of SEQ ID NO:2 and a light chain variable region that has the amino acid sequence of SEQ ID NO:4. 
     
     
       20. A method for treating an animal with cancer, comprising administering to said animal a therapeutically effective amount of a pharmaceutical composition comprising purified monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, or an antigen-binding fragment thereof. 
     
     
       21. The method of  claim 20 , wherein said pharmaceutical composition comprises said monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545. 
     
     
       22. The method of  claim 20 , wherein said pharmaceutical composition comprises said antigen-binding fragment of said monoclonal antibody 3G4 produced by hybridoma ATCC PTA 4545. 
     
     
       23. The method of  claim 22 , wherein said antigen-binding fragment of said monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, is operatively attached to a human antibody constant region. 
     
     
       24. The method of  claim 20 , wherein said animal is a human patient. 
     
     
       25. A method for treating an animal with cancer, comprising administering to said animal a therapeutically effective amount of a pharmaceutical composition comprising purified monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545. 
     
     
       26. The method of  claim 25 , wherein said animal is a human patient. 
     
     
       27. A method for inhibiting angiogenesis, comprising administering to an animal having a disease associated with angiogenesis a therapeutically effective amount of a pharmaceutical composition comprising purified monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, or an antigen-binding fragment thereof. 
     
     
       28. The method of  claim 27 , wherein said pharmaceutical composition comprises said monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545. 
     
     
       29. The method of  claim 27 , wherein said pharmaceutical composition comprises said antigen-binding fragment of said monoclonal antibody 3G4 produced by hybridoma ATCC PTA 4545. 
     
     
       30. The method of  claim 29 , wherein said antigen-binding fragment of said monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, is operatively attached to a human antibody constant region. 
     
     
       31. The method of  claim 27 , wherein said animal is a human patient. 
     
     
       32. A method for inhibiting angiogenesis, comprising administering to an animal having a disease associated with angiogenesis a therapeutically effective amount of a pharmaceutical composition comprising a purified antibody that comprises at least two variable regions that each comprises three CDRs, wherein said two variable regions are:
 (a) a heavy chain variable region that comprises a variable heavy (VH) CDR1, VH CDR2 and VH CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said variable heavy (VH) CDR1 has the amino acid sequence of SEQ ID NO:10, said VH CDR2 has the amino acid sequence of SEQ ID NO:11 and said VH CDR3 has the amino acid sequence of SEQ ID NO:12; and 
 (b) a light chain variable region that comprises a variabk light (VL) CDR1, VL CDR2 and VL CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said variable Ught (VL) CDR1 has the amino acid sequence of SEQ ID NO:13, said VL CDR2 has the amino acid sequence of SEQ ID NO:14 and said VL CDR3 has the amino acid sequence of SEQ ID NO:15. 
 
     
     
       33. The method of  claim 32 , wherein said animal has cancer. 
     
     
       34. The method of  claim 32 , wherein said heavy chain variable region has the amino acid sequence of SEQ ID NO:2. 
     
     
       35. The method of  claim 32 , wherein said light chain variable region has the amino acid sequence of SEQ ID NO:4. 
     
     
       36. The method of  claim 32 , wherein said antibody comprises a heavy chain variable region that has the amino acid sequence of SEQ ID NO:2 and a light chain variable region that has the amino acid sequence of SEQ ID NO:4. 
     
     
       37. The method of  claim 32 , wherein said animal is a human patient. 
     
     
       38. A method for treating an animal with cancer, comprising administering to said animal a therapeutically effective amount of a pharmaceutical composition comprising a purified antibody, or antigen-binding fragment thereof, that comprises at least two variable regions that each comprises three CDRs, wherein at least one of said variable regions is:
 (a) a heavy chain variable region from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, which has the amino acid sequence of SEQ ID NO:2; or 
 (b) a light chain variable region from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, which has the amino acid sequence of SEQ ID NO:4. 
 
     
     
       39. The method of  claim 38 , wherein said antibody or antigen-binding fragment thereof comprises said heavy chain variable region. 
     
     
       40. The method of  claim 38 , wherein said antibody or antigen-binding fragment thereof comprises said light chain variable region. 
     
     
       41. The method of  claim 38  wherein said antibody or antigen-binding fragment thereof comprises said heavy chain variable region and said light chain variable region. 
     
     
       42. The method of  claim 38 , wherein said animal is a human patient. 
     
     
       43. A method for inhibiting angiogenesis, comprising administering to an animal having a disease associated with angiogenesis a therapeutically effective amount of a pharmaceutical composition comprising a purified antibody, or antigen-binding fragment thereof, that comprises at least two variable regions that each comprises three CDRs, wherein at least one of said variable regions is:
 (a) a heavy chain variable region from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, which has the amino acid sequence of SEQ ID NO:2; or 
 (b) a light chain variable region from the monoctonal antibody 3G4, produced by hybridoma ATCC PTA 4545, which has the amino acid sequence of SEQ ID NO:4. 
 
     
     
       44. The method of  claim 43  wherein said antibody or antigen-binding fragment thereof comprises said heavy chain variable region. 
     
     
       45. The method of  claim 43  wherein said antibody or antigen-binding fragment thereof comprises said light chain variable region. 
     
     
       46. The method of  claim 43 , wherein said antibody or antigen-binding fragment thereof comprises said heavy chain variable region and said light chain variable region. 
     
     
       47. The method of  claim 43 , wherein said animal is a human patient. 
     
     
       48. The method of  claim 43 , wherein said pharmaceutical composition comprises said antigen-binding fragment of said antibody. 
     
     
       49. The method of  claim 48 , wherein said antigen-binding fragment of said antibody is operatively attached to a human constant domain.

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